Psilocybin for Healthy Subjects

Overseen By

Age: 18+

Sex: Any

Trial Phase: Phase 1 & 2

Sponsor: Johns Hopkins University

Must not be taking: Psychoactive medications, MAOIs

Disqualifiers: Pregnancy, Cardiovascular conditions, Epilepsy, others

Approved in 2 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: Unknown

Duration: 8 weeks

30 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial will study how psilocybin, a substance from certain mushrooms, affects thoughts and brain activity in healthy volunteers. Researchers will use computer tasks, EEG, and MRI to measure these effects. Understanding these changes may help improve future treatments and our knowledge of consciousness. Psilocybin, a psychoactive alkaloid found in hallucinogenic mushrooms, has been historically used for ritualistic, recreational, and medicinal purposes, with recent scientific interest in its potential therapeutic effects.

Will I have to stop taking my current medications?

If you are currently taking psychoactive prescription medications or medications with a primary serotonergic effect regularly, you will need to stop taking them before participating. For 'as needed' medications, there is a required waiting period before the psilocybin sessions.

Is psilocybin safe for human use?

Psilocybin, found in magic mushrooms, can cause effects like hallucinations and changes in movement, but is generally considered relatively harmless when used in controlled settings. However, there are risks if poisonous mushrooms are mistakenly consumed, and caution is advised for people with heart conditions. ^{1 2 3 4 5}

How is the drug psilocybin unique compared to other treatments?

Psilocybin is unique because it is a psychoactive compound found in 'magic mushrooms' that can induce hallucinogenic effects by rapidly affecting the central nervous system. Unlike traditional treatments, it is being studied for its potential to mediate beneficial health outcomes through the quality of the subjective experience it induces. ^{1 6 7 8 9}

What data supports the effectiveness of the drug psilocybin for healthy subjects?

Research indicates that psilocybin, found in magic mushrooms, can produce unique experiences by affecting serotonin receptors in the brain, which may lead to beneficial health outcomes. Although primarily studied in palliative care, its psychoactive effects are being explored for potential therapeutic applications. ^{1 2 8 10 11}

Who Is on the Research Team?

Frederick S Barrett, PhD

Principal Investigator

Johns Hopkins University

Are You a Good Fit for This Trial?

Participants must be healthy adults aged 18-75, vaccinated against COVID-19, fluent in English with at least high school education. They should have prior experience with psychedelics and agree to avoid psychoactive substances and certain medications before sessions. Pregnant or nursing women, individuals with cardiovascular issues, epilepsy, diabetes on insulin, psychiatric disorders or those taking serotonergic medications are excluded.

Inclusion Criteria

Have given written informed consent

Agree to refrain from using psychoactive drugs, alcoholic beverages, and nicotine within 24 hours of each drug administration

Agree not to take any 'as-needed' medications on the mornings of drug sessions

Exclusion Criteria

Left-handedness

Current or past history within the last five years of meeting DSM-5 criteria for moderate or severe alcohol or drug use disorder

I have diabetes that requires insulin or have had low blood sugar with diabetes pills.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive either psilocybin or placebo in a double-blind, placebo-controlled, within-subject, full cross-over study

8 weeks

Multiple visits for drug administration and assessments

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Placebo
• Psilocybin

Trial Overview The study examines the effects of psilocybin versus a placebo on thought processes and brain activity using EEG and MRI scans. Participants will perform computerized tasks while their brain responses are monitored to understand how this psychedelic compound affects them.

How Is the Trial Designed?

Group I: Psilocybin First Experimental Treatment 2 Interventions

Psilocybin (10mg) will be administered one time orally as a capsule taken with water. Expected duration of acute effects is approximately 6 hours. After a period of a washout, participants will switch to the placebo intervention.

Group II: Placebo First Placebo Group 2 Interventions

Participants will be administered placebo in a clinical setting. Placebo is administered orally as a capsule taken with water. After a period of a washout, participants will switch to the Psilocybin intervention.

Psilocybin is already approved in United States, European Union for the following indications:

Approved in United States as Psilocybin for:

• Treatment-resistant depression (TRD) under Breakthrough Therapy designation

Approved in European Union as Psilocybin for:

• Treatment-resistant depression (TRD) under PRIME designation

Who Is Running the Clinical Trial?

Johns Hopkins University

Lead Sponsor

Trials

2,366

Recruited

15,160,000+

Published Research Related to This Trial

Psilocybin shows promising effects in alleviating anxiety, depression, and emotional distress in palliative care patients, with a favorable safety profile, based on recent studies and reports.

Despite its potential benefits, psilocybin is not yet approved for therapeutic use in the U.S., and significant barriers exist for access, particularly for vulnerable populations like the elderly and those in palliative care.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Psilocybin in Palliative Care: An Update. Whinkin, E., Opalka, M., Watters, C., et al.[2023]

Psilocybin, a hallucinogenic compound found in certain mushrooms, has been associated with increasing rates of drug abuse, highlighting the need for comprehensive pharmacological understanding.

Despite its historical use in the 1960s for experimental medical purposes, recent research has only begun to uncover the pharmacological properties of psilocybin, indicating a gap in knowledge that needs to be addressed.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The pharmacology of psilocybin. Passie, T., Seifert, J., Schneider, U., et al.[2016]

This study found that the binding of serotonin 2A receptors (5-HT2AR) in the brain can predict how long the peak effects of psilocybin last and how quickly individuals return to normal consciousness after its effects wear off.

Higher levels of 5-HT2AR binding were associated with lower scores on the Mystical Experience Questionnaire, suggesting that individual differences in receptor availability may influence the subjective experience of psilocybin, which could have implications for its therapeutic use.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Brain serotonin 2A receptor binding predicts subjective temporal and mystical effects of psilocybin in healthy humans. Stenbæk, DS., Madsen, MK., Ozenne, B., et al.[2022]

Psilocybin-containing mushrooms, commonly known as hallucinogenic or 'magic' mushrooms, rapidly affect the central nervous system within 0.5-1 hour of ingestion, leading to effects such as ataxia, hyperkinesis, and hallucinations.

The review discusses the significant toxicity associated with these mushrooms, highlighting the need for awareness and understanding of their pharmacology, clinical effects, and potential treatment for adverse reactions.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Hallucinogenic mushrooms]. Reingardiene, D., Vilcinskaite, J., Lazauskas, R.[2018]

A meta-analysis of psilocybin studies found that higher doses of psilocybin are associated with stronger subjective experiences, particularly in areas like perceptual alterations and ego dissolution, based on data from standardized questionnaires.

Challenging experiences were less affected by dose, suggesting that individual and environmental factors also play a significant role in the psilocybin experience, indicating that these findings are most relevant in controlled settings rather than recreational use.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Dose-response relationships of psilocybin-induced subjective experiences in humans. Hirschfeld, T., Schmidt, TT.[2022]

A 30-year-old man experienced severe symptoms, including vomiting and muscle pain, after receiving an intravenous injection of Psilocybe mushroom extract, highlighting the potential dangers of using hallucinogenic substances in non-traditional ways.

The patient showed rapid improvement with supportive care, suggesting that while the effects of Psilocybe mushrooms can be serious, timely medical intervention can effectively manage the symptoms.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Intravenous mushroom poisoning. Curry, SC., Rose, MC.[2019]

There is a growing trend among young people to consume wild Psilocybin mushrooms for their hallucinogenic effects, but this practice carries risks.

The report highlights seven cases of mushroom overdosage, stressing that while Psilocybin mushrooms are generally considered harmless, there is a significant danger of accidentally consuming toxic mushroom species that can cause serious harm.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The danger of hallucinogenic mushrooms. Mills, PR., Lesinskas, D., Watkinson, G.[2017]

In a study examining the effects of Psilocybe cubensis and Panaeolus cyanescens mushrooms on heart cells, the extracts did not worsen hypertrophy caused by endothelin-1 and provided protection against TNF-α-induced cell injury.

The findings suggest that these mushroom extracts can be safely used in controlled conditions for potential therapeutic benefits in heart disease, although caution is advised with higher concentrations.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effects and safety of Psilocybe cubensis and Panaeolus cyanescens magic mushroom extracts on endothelin-1-induced hypertrophy and cell injury in cardiomyocytes. Nkadimeng, SM., Steinmann, CML., Eloff, JN.[2021]

A new liquid chromatography-tandem mass spectrometry (LC-MS/MS) method was developed to quickly and accurately measure the levels of psilocybin and psilocin in magic truffles, with high precision and reliability (r² > 0.99).

The study found that only psilocybin was present in the examined Psilocybe sclerotia, with concentrations ranging from 59.3 to 167.8 µg per 100 mg of fresh truffles, indicating variability in psilocybin content.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Magic truffles or Philosopher's stones: a legal way to sell psilocybin? Pellegrini, M., Rotolo, MC., Marchei, E., et al.[2019]

The study identified high levels of the psychoactive compounds psilocin and psilocybin in three species of mushrooms: Psilocybe semilanceata, Psilocybe bohemica, and Psilocybe arcana, indicating their potential for psychoactive effects.

Using gas chromatography-mass spectrometry (GC/MS) for quantification, the research provides a detailed analysis of the psilocin and psilocybin content in various mushroom species, contributing to the understanding of their psychoactive properties.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Levels of psilocybin and psilocin in various types of mushrooms]. Stríbrný, J., Borovicka, J., Sokol, M.[2016]

In a case study involving 'magic mushroom' intake, psilocin was detected in urine, primarily in its glucuronide form, indicating that enzymatic hydrolysis is essential for accurate analysis.

The study established a reliable GC-MS method for detecting psilocin, revealing that most of the psilocin in serum was also conjugated, with very low concentrations of free psilocin found in both urine and serum.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Detection of psilocin in body fluids. Sticht, G., Käferstein, H.[2019]

Citations

1. United States pubmed.ncbi.nlm.nih.gov

Psilocybin in Palliative Care: An Update. [2023]

2. United States pubmed.ncbi.nlm.nih.gov

The pharmacology of psilocybin. [2016]

3. United States pubmed.ncbi.nlm.nih.gov

Brain serotonin 2A receptor binding predicts subjective temporal and mystical effects of psilocybin in healthy humans. [2022]

4. Switzerland pubmed.ncbi.nlm.nih.gov

[Hallucinogenic mushrooms]. [2018]

5. United States pubmed.ncbi.nlm.nih.gov

Dose-response relationships of psilocybin-induced subjective experiences in humans. [2022]

6. United States pubmed.ncbi.nlm.nih.gov

Intravenous mushroom poisoning. [2019]

7. Scotland pubmed.ncbi.nlm.nih.gov

The danger of hallucinogenic mushrooms. [2017]

8. England pubmed.ncbi.nlm.nih.gov

Effects and safety of Psilocybe cubensis and Panaeolus cyanescens magic mushroom extracts on endothelin-1-induced hypertrophy and cell injury in cardiomyocytes. [2021]

9. England pubmed.ncbi.nlm.nih.gov

Magic truffles or Philosopher's stones: a legal way to sell psilocybin? [2019]

10. Czech Republic pubmed.ncbi.nlm.nih.gov

[Levels of psilocybin and psilocin in various types of mushrooms]. [2016]

11. Ireland pubmed.ncbi.nlm.nih.gov

Detection of psilocin in body fluids. [2019]